Diabetes mellitus is a major health epidemic categorized into two subclasses: type 1, known as insulin dependent diabetes mellitus (IDDM), and type 2, noninsulin dependent diabetes mellitus (NIDDM).1 Type 2 diabetes is a chronic and progressive metabolic disorder of carbohydrate and lipid metabolism and accounts for nearly 90% of diabetes mellitus and results from impaired insulin secretion and reduced peripheral insulin sensitivity—a burgeoning, worldwide health problem affecting almost twenty-six million people in the United States.2 Current oral therapies for this disease are limited by availability of effective medications, including, for example, insulin secretagogues, such as sulfonylureas; activators of the peroxisome proliferator-activated receptor-γ (“PPAR-γ”) such as the thiazolidinediones; and effectors of glucose-lowering, exemplified by metformin and its analogues. All of the existing oral hypoglycemic agents have subsequent failure after long term administration. Deficiencies associated with currently available treatments include hypoglycemic episodes, weight gain, gastrointestinal problems, edema, and loss of responsiveness over time.
Metformin is a commonly used medication in the treatment of diabetes. Recent interest in metformin as a potential anticancer agent has sparked studies suggesting cancer patients with or without diabetes may benefit in lowering insulin levels. The currently marketed metformin hydrochloride salt was approved by the United States Food and Drug Administration (FDA) in 1995 as an oral hypoglycemic agent. Given alone or in combination with a sulfonylurea and insulin, metformin reduces hyperglycemia through decreased hepatic glucose output and enhanced glucose uptake by skeletal muscle. However, metformin HCl has poor oral bioavailability (only about 50%) because of its poor absorption from lower gastrointestinal tract. Thus there is a need in the art to develop new therapies for diabetes and cancer as well as a need to develop compositions having greater bioavailability to patients suffering from diabetes and its associated diseases, and cancer. Provided herein are solutions to these and other problems in the art.